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Simple Summary: Bemisia tabaci Middle East–Asia Minor I (MEAM1) is a widely distributed invasive agricultural pest that causes extensive damage to agricultural, horticultural, and ornamental crops. Laccase2 (Lac2), a phenol oxidase, plays an important role in cuticle tanning of some insects. However, the function of Lac2 in whitefly remains unclear. In this study, we identified a BtLac2 gene in MEAM1 that is expressed in all developmental stages, and its expression in the cuticle is especially high. Knockdown of BtLac2 in nymphs produced thinner and fragile cuticles, which significantly increased the mortality rate and extended the development duration of nymphs, as well as further decreasing the emergence rate of adults. Overall, BtLac2 plays an important role in cuticle hardening of whitefly, suggesting a potential management strategy using RNAi to knock down BtLac2 expression. Cuticle sclerotization is critical for insect survival. Laccase2 (Lac2) is a phenol oxidase that plays a key role in cuticle formation and pigmentation in a variety of insects. However, the function of Lac2 in whitefly, Bemisia tabaci, remains unclear. In this study, we identified a BtLac2 gene in B. tabaci MEAM1 and found that BtLac2 was expressed in all stages. It was highly expressed in the egg stage, followed by nymph and adult. Moreover, the expression of BtLac2 was higher in the cuticle than in other tissues. Knockdown of BtLac2 in nymphs produced thinner and fragile cuticles, which significantly increased the mortality rate, extended the development duration of nymphs, and decreased the emergence rate of adults. This result demonstrates that BtLac2 plays an important role in the cuticle hardening of B. tabaci and suggests a potential management strategy using RNAi to knock down BtLac2 expression. [ABSTRACT FROM AUTHOR]